chr19-812701-C-A

Variant names:

• chr19-812701-C-A
• rs1345715872
• NM_001270366.2:c.2026G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001270366.2(PLPPR3):​c.2026G>T​(p.Ala676Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 1,051,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A676E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: PLPPR3 NM_001270366.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.389
• Publications: 0 publications found

Genes affected

PLPPR3 (HGNC:23497): (phospholipid phosphatase related 3) The proteins in the lipid phosphate phosphatase (LPP) family, including PRG2, are integral membrane proteins that modulate bioactive lipid phosphates including phosphatidate, lysophosphatidate, and sphingosine-1-phosphate in the context of cell migration, neurite retraction, and mitogenesis (Brauer et al., 2003 [PubMed 12730698]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044363797).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270366.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPPR3	NM_001270366.2	MANE Select	c.2026G>T	p.Ala676Ser	missense	Exon 8 of 8	NP_001257295.1	Q6T4P5-1
	PLPPR3	NM_024888.3		c.2110G>T	p.Ala704Ser	missense	Exon 7 of 7	NP_079164.1	Q6T4P5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPPR3	ENST00000520876.8	TSL:1 MANE Select	c.2026G>T	p.Ala676Ser	missense	Exon 8 of 8	ENSP00000430297.1	Q6T4P5-1
	PLPPR3	ENST00000359894.6	TSL:1	c.2110G>T	p.Ala704Ser	missense	Exon 7 of 7	ENSP00000352962.2	Q6T4P5-3
	PLPPR3	ENST00000947290.1		c.2110G>T	p.Ala704Ser	missense	Exon 6 of 6	ENSP00000617349.1

Frequencies

GnomAD3 genomes AF: 0.0000409 AC: 6 AN: 146766 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000677

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000758

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000232 AC: 21 AN: 904564 Hom.: 0 Cov.: 35 AF XY: 0.0000165 AC XY: 7 AN XY: 423036

African (AFR) AF: 0.0000593 AC: 1 AN: 16860

American (AMR) AF: 0.00 AC: 0 AN: 2924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6830

East Asian (EAS) AF: 0.00 AC: 0 AN: 9496

South Asian (SAS) AF: 0.00 AC: 0 AN: 18248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10918

Middle Eastern (MID) AF: 0.000515 AC: 1 AN: 1942

European-Non Finnish (NFE) AF: 0.0000223 AC: 18 AN: 806080

Other (OTH) AF: 0.0000320 AC: 1 AN: 31266

GnomAD4 genome AF: 0.0000409 AC: 6 AN: 146766 Hom.: 0 Cov.: 32 AF XY: 0.0000560 AC XY: 4 AN XY: 71386

African (AFR) AF: 0.00 AC: 0 AN: 40922

American (AMR) AF: 0.0000677 AC: 1 AN: 14772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3394

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8488

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000758 AC: 5 AN: 66000

Other (OTH) AF: 0.00 AC: 0 AN: 2020

Alfa AF: 0.000162 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.0
DANN	Benign	0.96
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.39
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.079
Sift	Benign	1.0	T
Sift4G	Benign	0.89	T
Polyphen		0.073	B
Vest4		0.12
MutPred		0.10		Gain of glycosylation at A676 (P = 0.0095)
MVP		0.17
MPC		0.37
ClinPred		0.17	T
GERP RS		3.6
Varity_R		0.074
gMVP		0.20
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1345715872; hg19: chr19-812701;